Galectins-1, -3 and -9, are endowed with many immune-regulatory properties, with galectins-1 and -9 largely regarded as anti-inflammatory and galectin-3 as pro-inflammatory. Expression levels increase in activated adaptive immune cells, with peak expression often correlating with peak inflammation. Galectin actions are not only determined by their expression levels but also target tissue permissibility to galectin binding, which is in turn determined by the profile of specific carbohydrate residues, namely N-acetyllactosamine, recognised by these lectins. How expression levels and actions are modulated in innate immune cells during inflammation has not been systematically characterised. This study therefore set out to delineate the effects of inflammation on neutrophil glycophenotype, as well as elucidate the temporal and spatial modulation of galectins during resolving inflammation. The neutrophil glycophenotype was modulated during trafficking with decreased levels of all terminal glycan residues assessed. However, this did not correlate with galectin binding permissibility suggesting this is not a useful indicator in this model. The overall change in glycosylation may theoretically be a consequence of rapid modulation of cell surface glycoproteins by activated neutrophils (i.e. CD62L shedding) rather than the actions of specific glycosylation enzymes as demonstrated in T- and endothelial cells. Assessment of galectin levels in leukocytes over a 96h zymosan-induced resolving peritonitis demonstrated alterations both spatially and temporally with increased galectin-3 expression in neutrophils at the inflammatory site compared to the periphery and a peak expression at 24h adding supporting evidence that modulation of galectin expression allows delineation of galectin responses by neutrophils. This study also demonstrated a novel pro-resolution effect of galectin-3 with defective resolution observed in galectin-3 null mice. In conclusion this work demonstrated that neutrophil permissibility for galectins-1, -3 and -9 binding is more likely a consequence of the exposure to galectins at specific time points in the resolving inflammatory response rather than due to a modulation of the glycophenotype upon activation. This study also 3 demonstrated that as well as an important role in the induction of an inflammatory response galectin-3 is involved in resolution, a novel finding which may lead to a better understanding of the resolution process.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:667458 |
| Date | January 2015 |
| Creators | Wright, Rachael Deborah |
| Publisher | Queen Mary, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://qmro.qmul.ac.uk/xmlui/handle/123456789/9014 |
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